Methylated polynuclear aromatic hydrocarbons are important environmental carcinogens, which are particularly abundant in materials related to synthetic fuels and in cigarette smoke. A better understanding of the structural requirements for carcinogenicity and mutagenicity of these compounds is essential for assessment of their hazards to man. In our studies, the major pathways of metabolic activation of 5-methylchrysene, the only highly carcinogenic methylchrysene isomer, have been determined. Based on this work, structural requirements favoring the carcinogenicity of other methylated polynuclear aromatic hydrocarbons have been developed. The requirements are the presence of a bay region methyl group and free peri position both adjacent to an unsubstituted angular ring. In the present proposal, the mechanistic basis for the enhancing effect on carcinogenicity of a bay region methyl group and the inhibiting effect of a substituted peri position will be determined. The structural requirements for carcinogenicity will be evaluated further by the synthesis and bioassay of specific methylated isomers of benzo(b)fluoranthene and benzo(j)fluoranthene. These studies will solidify our understanding of the mechanism of action of methylated polynuclear aromatic hydrocarbons and will allow more accurate prediction of the effects of methyl substitution in other polynuclear aromatic hydrocarbon systems.